Hepatocellular carcinoma (HCC) accounts for the third leading cause of cancer-associated deaths worldwide. Microwave ablation (MWA) is an emerging minimally invasive treatment against early HCC. Unfortunately, many HCC patients suffer from tumor metastasis/recurrence after MWA treatment possibly ascribed to the tumor-promoting inflammation induced by MWA. Herein, we report the development of a multifunctional hydrogel (termed DDOC) for efficient complementary treatment of HCC after MWA. The DDOC hydrogel is constructed by loading dexamethasone (Dex) into the self-assembled doxorubicin (Dox)-grafted oxidized sodium alginate (Dox-OSA) micelles, followed by cross-linking with Ca2+. Upon intratumoral injection of the DDOC hydrogel, the unencapsulated Dex in the hydrogel matrix can be rapidly released for efficient alleviation of the tumor-promoting inflammation. Then, the encapsulated Dex in the micellar core can be slowly released for regulation of glucose metabolism in tumor, achieving remodeling of the immunosuppressive microenvironment. Moreover, the chemodrug Dox can be gradually released to induce sustained immunogenic cell death for continuous anticancer immunity activation. In vivo experiments on humanized cell line-derived xenograft tumor model demonstrated remarkable therapeutic outcome of the combinational "DDOC + MWA" treatment. This work offers a feasible solution for inhibiting tumor metastasis and recurrence after MWA therapy in clinic.
[1]Southeast Univ, Sch Biol Sci & Med Engn, State Key Lab Digital Med Engn, Jiangsu Key Lab Biomat & Devices, 2 Southeast Univ Rd, Nanjing 211189, Peoples R China.
[2]Southeast Univ, Sch Med, Zhongda Hosp, Nanjing 210009, Peoples R China.
[3]Wannan Med Coll, Affiliated Hosp 1, Wuhu 241000, Anhui, Peoples R China.
[4]Nanjing Med Univ, Affiliated Hosp 1, Dept Intervent Radiol, Nanjing 210029, Peoples R China.
(8.0+极速模式)